Benchmarking Adaptive Steered Molecular Dynamics (ASMD) on CHARMM Force Fields

Abstract

The potentials of mean force (PMFs) along the end‐to‐end distance of two different helical peptides have been obtained and benchmarked using the adaptive steered molecular dynamics (ASMD) method. The results depend strongly on the choice of force field driving the underlying all‐atom molecular dynamics, and are reported with respect to the three most popular CHARMM force field versions: c22, c27 and c36. Two small peptides, ALA10 and 1PEF, serve as the particular case studies. The comparisons between the versions of the CHARMM force fields provides both a qualitative and quantitative look at their performance in forced unfolding simulations in which peptides undergo large changes in structural conformations. We find that ASMD with the underlying c36 force field provides the most robust results for the selected benchmark peptides.

Tertiary Plasticity Drives the Efficiency of Enterocin 7B Interactions with Lipid Membranes

“…The solvated systems were then neutralized with Na and Cl ions. Subsequently, a three-step equilibration procedure is performed using Scalable MD (NAMD) and our ASMD scripts to obtain the equilibrated system. First, the whole system is equilibrated for 5 ns under NPT conditions at 300 K. The Nosé–Hoover Langevin piston method is applied to maintain the pressure at 1 atm with a decay period of 100 fs, a damping time constant of 50 fs and a damping coefficient as 5 ps –1 .…”

Correlation between chemical denaturation and the unfolding energetics of Acanthamoeba actophorin

“…The CHARMM36 force field was used to model the interaction forces because they have been seen to provide significant improvement in the prediction of the and dihedral interaction energies through the CMAP correction terms generally ( 65 , 66 ), and in ASMD in particular ( 67 ). A 2 fs timestep was chosen assuming that the vibration of hydrogen atoms can be ignored without affecting the PMF calculation.…”

Mechanism of Phosphate Release from Actin Filaments

“…The rate limiting step in their simulations was dissociation of phosphate from the divalent cation in the active site, assumed to be Ca 2+ rather than the physiological Mg 2+ . However, as pointed out by more recent studies (31-33), SMD can produce slow-converging, significantly out of equilibrium trajectories, potentially less representative of physiological molecular dynamics. Cryo-EM structures of actin filaments with bound AMPPNP (an ATP analog)-, ADP-P i -, and ADP-actin filaments nucleotides suggested a possible exit gate formed by R177, N111, and HIC73, which was closed in the ADP-P i -actin structure and open in the ADP-actin structure.…”

“…The rate limiting step in their simulations was dissociation of phosphate from the divalent cation in the active site, assumed to be Ca 2+ rather than the physiological Mg 2+ . However, as pointed out by more recent studies (31)(32)(33), SMD can produce slow-converging, significantly out of equilibrium trajectories, potentially less representative of physiological molecular dynamics.…”